Macroporous hydrogels for tissue engineering scaffolds are ideally formed from a water-soluble polymer such as poly(ethylene glycol) (PEG). One problem with pure PEG hydrogels as scaffolds, however, is that it can be difficult for cells to infiltrate and degrade them due to their density and homogeneity at the cell scale. Macroporous hydrogels, therefore, are desirable but require incorporation of a pore-forming substance (porogen), which may be difficult to control (e.g., a foaming agent) or remove (e.g., poly(methylmethacrylate) microbeads). Porous hydrogels may become mechanically weak if porosity reaches a high degree, but a high degree of porosity is desirable for cell migration into the scaffold so that pores are highly connected. Materials that are strong enough to be highly porous typically have poor biocompatibility compared to hydrogels. Cell migration into the scaffold is desirable in the generation of new functional tissues induced by implanted biomaterials.
In one example, peripheral nerve regeneration is a complex problem that, despite many advancements and innovations, still has sub-optimal outcomes. Compared to biologically derived acellular nerve grafts and autografts, completely synthetic nerve guidance conduits (NGC), which allow for precise engineering of their properties, are promising but still far from optimal. If the conduit contains a homogenous degradable material, cells may dissolve the material uniformly but too slowly or too quickly to allow rapid cell migration.
Therefore, there is a need for creating multifunctional macroporous hydrogel scaffolds with microscale gradients in cell-initiated degradability to provide pathways for cell migration.